We are studying the assembly of bacterial viruses, by identifying the genes and proteins involved in assembly processes, and the protein- protein interactions which result in the formation of complex structures. The experiments concentrate on 1) the formation of the head of the temperature generalized transducing phage P22 of Salmonella and 2) on the assembly of the contractile tail of bacteriophage T4. Of particular interest in P22 assembly is the participation of a catalytic scaffolding protein in shell formation. Scaffolding protein copolymerizes with coat protein to yield a precursor shell containing both proteins. In concert with DNA packaging all the scaffolding molecules exit from the precursor shell and then recycle to catalyze further shell assembly. The assembly of the phage tail requires the products of 21 phage genes. We are trying to identify all the morphological intermediates in tail assembly and the nature of the sequential assembly process. All the reactions proceed in vitro, providing a very useful activity assay for structural proteins. The proteins seem to be synthesized in a form in which they don't spontaneously assemble. There is no proteolytic cleavage, rather the proteins are activated by incorporation into a preformed intermediate structure, which then becomes the active substrate for the next protein in the pathway.